Preparation process of silybin meglumine tablet

Abstract

The invention discloses a preparation method of a silybin meglumine tablet, which comprises the following steps: reacting silybin with meglumine under optimized conditions to generate a liquid reactant, omitting a drying link, and directly adding the liquid reactant into an auxiliary material through spray gun atomization for one-step granulation; the auxiliary materials are screened and premixed, and after liquid reactants and the auxiliary materials are uniformly mixed, the temperature and spraying parameters are controlled to complete particle preparation. And after granulation, drying to a target water content by adopting fluidized bed drying equipment, and carrying out particle mixing, tabletting and coating to finally finish aluminum-plastic subpackaging and outer packaging. The process omits the traditional steps of drying, crushing and granulating, prevents reactants from being exposed to a high-temperature environment for a long time, and effectively improves the utilization rate of raw materials, the content of effective components and the purity of the product. Meanwhile, dust is reduced, the production environment is optimized, and the operation safety and the product yield are remarkably improved.

Description

Technical Field

[0001] The invention relates to the field of medicine, and more specifically to a preparation process of silybin meglumine tablets. Background Art

[0002] Silybin meglumine is an important active ingredient in medicines and is widely used in the field of liver protection. In the existing preparation process, the granulation process usually adopts the wet granulation method, that is, silybin meglumine is mixed with excipients and then wet granulated to prepare granules. However, this traditional process has the following problems:

[0003] (1) Dust problem

[0004] After wet granulation, the granules need to be dried and granulated. In this process, if there is a lack of efficient dust collection measures, a lot of dust will be generated in the production area, which will not only cause material loss, but also pose a potential threat to the health of production operators.

[0005] (2) Thermal decomposition risk

[0006] Silybin meglumine raw materials are extremely sensitive to heat and are easily decomposed during drying and subsequent high-temperature operations, resulting in a decrease in the effective content of the raw materials. This decomposition phenomenon not only affects the utilization rate of the raw materials, but also significantly reduces the yield and quality of the finished products.

[0007] In view of the above problems, the existing process needs to be further optimized to reduce dust pollution, improve production efficiency, and enhance product quality and yield. Summary of the invention

[0008] In order to solve the deficiencies of the prior art, the present invention provides a preparation process of silybin meglumine tablets, and the specific scheme is as follows:

[0009] A preparation process of silybin meglumine tablets, the preparation process comprising the following steps:

[0010] S1. Selection of raw materials and solvents: Silybin and solvent are mixed in a mass ratio of 1:10; a 20% by mass fraction of meglumine solution is used for the reaction;

[0011] S2. Prepare auxiliary materials: the mass percentage of auxiliary materials is 30-50% microcrystalline cellulose, 20-30% lactose, 5-10% hydroxypropyl methylcellulose, 5-10% low-substituted hydroxypropyl cellulose and 0.5-1% magnesium stearate;

[0012] S3, one-step granulation: use a one-step granulator to complete the preparation of granules; add the auxiliary material mixture into the mixing chamber for mixing; atomize the liquid reactant through a spray gun and evenly spray it into the auxiliary material; control the temperature of the granulation chamber at 25-35°C to avoid the reactant from decomposing due to high temperature; after the spraying is completed, continue to stir and granulate for 5-10 minutes until the granules are uniformly formed; the wet granules have a particle size range of 200-400 μm;

[0013] S4: Processing the wet granules using a fluidized bed drying device;

[0014] S5. Granule mixing: The dried granules and 0.5-1% magnesium stearate are stirred in a mixer for 2-3 minutes; a high-speed rotary tablet press is used, and the tableting pressure is controlled at 8-10 MPa; the molding time is 0.5-1 second, and the weight deviation of a single tablet does not exceed ±3%;

[0015] S6. Coating: Coating the tablets in a coating machine with a spraying rate controlled at 10-15 mL / min;

[0016] S7. Outer packaging after aluminum-plastic packaging: Use an automatic aluminum-plastic packaging machine to complete the sealed packaging, and then put it into the outer packaging box.

[0017] Furthermore, in S1, silybin and a solvent are added to a reactor, the stirring speed is set to 300-500 rpm, the temperature is controlled at 25-30° C., and the dissolution time is 2-3 hours; the meglumine solution is added in batches, and the amount added each time does not exceed 20% of the total solution, and the solution temperature is kept stable during the stirring process; the mixed solution is reacted at 25-30° C. for 3-5 hours to ensure that silybin and meglumine are fully reacted to form silybin meglumine liquid reactant; the reaction impurities are removed by vacuum decompression filtration, and the reactant solution after filtration is set aside, and the content in the liquid is required to reach ≥98%.

[0018] Furthermore, all auxiliary materials in S2 are sieved through a 200-mesh sieve; and premixed using a V-type mixer for 10 to 15 minutes to ensure uniform distribution.

[0019] Furthermore, the speed of the mixer in the mixing chamber of S3 is set to 120-180 rpm; the spray pressure of the spray gun is controlled at 0.1-0.3 MPa, and the spray rate is 5-10 mL / min.

[0020] Furthermore, in S4, the initial temperature is set at 40-50°C, and gradually increased to 55-60°C; the drying time is 20-30 minutes, until the moisture content of the particles is less than 3%.

[0021] Furthermore, the coating solution in S6 is composed of hydroxypropyl methylcellulose, polyethylene glycol and purified water; all components are stirred and dissolved in a water bath at 50-60° C., and are cooled and set aside.

[0022] Furthermore, the temperature of the coating chamber in S6 is controlled at 35-45° C., and the coating time is about 30 minutes.

[0023] Furthermore, the packaging temperature in S7 is set to 120-130°C.

[0024] Beneficial effects:

[0025] This patent provides an optimized preparation process for silybin meglumine tablets, which significantly reduces dust pollution and material waste by simplifying the process and accurately controlling each link, while improving production efficiency and finished product yield. First, this process eliminates the drying, crushing and mixing steps in the preparation process of the raw material silybin meglumine, and directly uses liquid reactants to complete granulation through a one-step granulation device. This not only simplifies the production process and shortens the production cycle, but also greatly reduces the exposure time of the raw materials in a high temperature environment, effectively reduces the thermal decomposition of silybin, and improves the content of effective ingredients and product purity. Through the optimized auxiliary material mixing, tableting, coating and packaging processes, the tablets are uniform in quality, beautiful in appearance, and strong in stability, meeting the dual needs of efficient production and patient acceptance. In addition, the process is environmentally friendly, has low energy consumption, is suitable for the high standards of the modern pharmaceutical industry, and has good promotion and application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The present invention is a flow chart of a preparation process of silybin meglumine tablets. DETAILED DESCRIPTION

[0027] In order to deepen the understanding of the present invention, the present invention will be further described in detail below in conjunction with examples. The examples are only used to explain the present invention and do not constitute a limitation on the protection scope of the present invention.

[0028] Example:

[0029] Figure 1 The present invention is a flow chart of the preparation process of silybin meglumine tablets, such as Figure 1 As shown, a preparation process of silybin meglumine tablets comprises the following steps:

[0030] 1. Selection and reaction of raw materials and solvents

[0031] In a 50L reactor, add 5kg of silybin and 50L of solvent (ethanol, purity ≥99%) at a mass ratio of 1:10. Set the stirring speed to 400rpm, control the temperature at 28°C, and dissolve for 2.5 hours until the silybin is completely dissolved.

[0032] Prepare 20% meglumine solution and add it in five times, each adding amount is 20% of the total solution, and the interval time is 20 minutes. Keep the temperature of the reaction solution at 25-30°C during stirring.

[0033] The mixed solution is reacted at 28°C for 4 hours to ensure that silibinin and meglumine react completely to form silibinin meglumine liquid reactant. After the reaction is completed, impurities are removed by vacuum decompression filtration, and the content of the obtained liquid reactant is ≥98%. This liquid reactant is directly used for subsequent granulation without drying.

[0034] By controlling the low temperature and adding meglumine in batches, the decomposition of silybin due to high temperature exposure is avoided, thereby ensuring the purity and yield of the reaction product.

[0035] 2. Preparation of auxiliary materials

[0036] Excipient selection: microcrystalline cellulose 40%, lactose 25%, hydroxypropyl methylcellulose 7%, low-substituted hydroxypropyl cellulose 8%, and magnesium stearate 0.8%.

[0037] All auxiliary materials were sieved through a 200-mesh screen and mixed using a V-type mixer. The mixing time was 12 minutes and the mixing speed was set at 60 rpm to ensure uniform distribution of the auxiliary materials.

[0038] The screening and uniform mixing of excipients ensures the consistency of subsequent granule quality and effectively reduces the uneven distribution of ingredients in the granules.

[0039] 3. One-step granulation

[0040] Using a one-step granulator, the auxiliary material mixture was first added into the mixing chamber of the granulator, and the speed in the mixing chamber was set to 150 rpm.

[0041] The liquid silybin meglumine reactant was uniformly sprayed into the auxiliary materials through a spray gun, the spray gun spray pressure was controlled at 0.2 MPa, and the spray rate was 8 mL / min. During the spraying process, the temperature of the granulation chamber was controlled at 30°C.

[0042] After spraying, mixing was continued for 8 minutes, and the particle size of the wet particles was controlled within the range of 200 to 400 μm.

[0043] One-step granulation eliminates the drying and granulation steps in traditional wet granulation, while avoiding the loss of materials at high temperatures and significantly reducing dust pollution.

[0044] 4. Drying

[0045] The wet granules were dried by fluidized bed drying equipment, with the initial temperature set at 45°C and gradually raised to 55°C for 25 minutes until the moisture content of the granules was less than 3%.

[0046] The temperature-controlled drying process reduces the thermal decomposition of silybin meglumine and improves the stability and active ingredient content of the particles.

[0047] 5. Tablet pressing

[0048] The dried granules were mixed with 0.8% magnesium stearate in a mixer for 3 minutes to ensure that the lubricant was evenly distributed.

[0049] The tablets were pressed using a high-speed rotary tablet press, with the tableting pressure set at 9 MPa and the molding time at 0.8 seconds. After the tableting was completed, the weight deviation of a single tablet did not exceed ±3%.

[0050] By optimizing tableting pressure and time, the tablets are well formed and free of cracks, thus improving the quality of the finished product.

[0051] 6. Coating

[0052] Preparation of coating solution: Dissolve 6% hydroxypropyl methylcellulose and 1.5% polyethylene glycol in purified water, stir in a 55°C water bath for 30 minutes, and set aside after cooling.

[0053] Use a coating machine for film coating, the spraying rate is controlled at 12 mL / min, the coating chamber temperature is maintained at 40°C, and the coating time is 30 minutes.

[0054] By optimizing the ratio of coating liquid, the coated tablets have a smooth appearance, uniform dissolution rate and improved stability.

[0055] 7. Packaging

[0056] The coated tablets are sealed and packaged by an automatic aluminum-plastic packaging machine, and the packaging temperature is set at 125°C to complete the aluminum-plastic sealing.

[0057] Finally, the tablets are packed into an outer box along with instructions for use.

[0058] In this embodiment, the preparation process of silybin meglumine is optimized, and parameters are carefully controlled from raw material processing to finished product packaging, so that the yield of the final product is increased by about 10%, and the content of the active ingredient is stabilized at more than 98%. At the same time, the one-step granulation technology reduces the production steps, significantly reduces dust pollution, and improves the environmental protection and economy of the process.

[0059] As a further improvement, the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A preparation process of silybin meglumine tablets, characterized in that: The preparation process comprises the following steps: S1. Selection of raw materials and solvents: Silybin and solvent are mixed in a mass ratio of 1:10; a 20% mass fraction of meglumine solution is used for the reaction; S2. Prepare auxiliary materials: the mass percentage of auxiliary materials is 30-50% microcrystalline cellulose, 20-30% lactose, 5-10% hydroxypropyl methylcellulose, 5-10% low-substituted hydroxypropyl cellulose and 0.5-1% magnesium stearate; S3, one-step granulation: use a one-step granulator to complete the preparation of granules; add the auxiliary material mixture into the mixing chamber for mixing; atomize the liquid reactant through a spray gun and evenly spray it into the auxiliary material; control the temperature of the granulation chamber at 25-35°C to avoid the reactant from decomposing due to high temperature; after the spraying is completed, continue to stir and granulate for 5-10 minutes until the granules are uniformly formed; the wet granules have a particle size range of 200-400 μm; S4: Processing the wet granules using a fluidized bed drying device; S5. Granule mixing: The dried granules and 0.5-1% magnesium stearate are stirred in a mixer for 2-3 minutes; a high-speed rotary tablet press is used, and the tableting pressure is controlled at 8-10 MPa; the molding time is 0.5-1 second, and the weight deviation of a single tablet does not exceed ±3%; S6. Coating: Coating the tablets in a coating machine with a spraying rate controlled at 10-15 mL / min; S7. Outer packaging after aluminum-plastic packaging: Use an automatic aluminum-plastic packaging machine to complete the sealed packaging, and then put it into the outer packaging box.

2. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: In S1, silybin and solvent are added to a reactor, the stirring speed is set to 300-500 rpm, the temperature is controlled at 25-30° C., and the dissolution time is 2-3 hours; the meglumine solution is added in batches, and the amount added each time does not exceed 20% of the total solution, and the solution temperature is kept stable during the stirring process; the mixed solution is reacted at 25-30° C. for 3-5 hours to ensure that silybin and meglumine are fully reacted to generate silybin meglumine liquid reactant; the reaction impurities are removed by vacuum decompression filtration, and the reactant solution after filtration is used for standby use, and the content in the liquid is required to reach ≥98%.

3. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: All auxiliary materials in S2 were sieved through a 200-mesh sieve; they were premixed using a V-type mixer for 10 to 15 minutes.

4. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: The mixer speed in the mixing chamber of S3 is set to 120-180 rpm; the spray pressure of the spray gun is controlled at 0.1-0.3 MPa, and the spray rate is 5-10 mL / min.

5. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: In S4, the initial temperature is set at 40-50°C and gradually increased to 55-60°C; the drying time is 20-30 minutes until the moisture content of the particles is less than 3%.

6. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: The coating solution in S6 is composed of hydroxypropyl methylcellulose, polyethylene glycol and purified water; all components are stirred and dissolved in a water bath at 50-60°C and cooled for use.

7. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: The temperature of the coating chamber in S6 is controlled at 35-45°C, and the coating time is about 30 minutes.

8. The preparation process of silybin meglumine tablets according to claim 1, characterized in that: The packaging temperature in S7 is set to 120-130°C.

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